Chemical Biology & Drug Design

Cover image for Vol. 78 Issue 6

December 2011

Volume 78, Issue 6

Pages i–iii, 907–1034

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. Editorial
    4. Review
    5. Research Articles
    6. Research Letters
    1. Issue Information (pages i–iii)

      Version of Record online: 16 NOV 2011 | DOI: 10.1111/j.1747-0285.2011.01260.x

  2. Editorial

    1. Top of page
    2. Issue Information
    3. Editorial
    4. Review
    5. Research Articles
    6. Research Letters
  3. Review

    1. Top of page
    2. Issue Information
    3. Editorial
    4. Review
    5. Research Articles
    6. Research Letters
    1. You have free access to this content
      Dz13: c-Jun Downregulation and Tumour Cell Death (pages 909–912)

      Mina Elahy and Crispin R. Dass

      Version of Record online: 31 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01166.x

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      Dz13, a deoxyribozyme, has been found to have efficacious effects against tumours directly and indirectly, for instance against tumour-induced angiogenesis. DzM14, a shorter version of Dz13, has anticancer activity as well, though the mechanism of activity is different to Dz13.

  4. Research Articles

    1. Top of page
    2. Issue Information
    3. Editorial
    4. Review
    5. Research Articles
    6. Research Letters
    1. Identification of Novel Antitubulin Agents by Using a Virtual Screening Approach Based on a 7-Point Pharmacophore Model of the Tubulin Colchi-Site (pages 913–922)

      Alberto Massarotti, Sewan Theeramunkong, Ornella Mesenzani, Antonio Caldarelli, Armando A. Genazzani and Gian Cesare Tron

      Version of Record online: 31 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01245.x

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      An intensive search for new antimicrotubule agents has occurred. Indeed, in silico models have been presented that might aid the discovery of novel agents. Among these, a 7-point pharmacophore model has been recently proposed. As a formal proof of this model, we carried out a ligand-based virtual screening on the colchicine binding site. In vitro testing demonstrated that two compounds displayed a cytotoxic profile on neuroblastoma cancer cells (SH-SY5H) and one had an antitubulinic profile.

    2. Human Placental Alkaline Phosphatase-Mediated Hydrolysis Correlates Tightly with the Electrostatic Contribution from Tail Group (pages 923–931)

      Yongliang Yang, Ketai Wang, Wentao Li, S. James Adelstein and Amin I. Kassis

      Version of Record online: 24 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01238.x

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      Human placental alkaline phosphatase (PLAP) has been identified as a hydrolase that is significantly overexpressed on the surface of solid tumor cells, thereby a suitable prodrug design targets for non-invasive cancer imaging and therapy. We have been probing the catalytic proficiency of PLAP towards several substrate structures experimentally and correlating these results to in silico predictions. We have found that electrostatic contribution from the tail group is the most crucial factor to determine the catalytic efficiencies of the substrates.

    3. Design, Synthesis, and In vitro Antitumor Activity Evaluation of Novel 4-pyrrylamino Quinazoline Derivatives (pages 932–940)

      Xiaoqing Wu, Mingdong Li, Wenhua Tang, Youguang Zheng, Jiqin Lian, Liang Xu and Min Ji

      Version of Record online: 24 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01234.x

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      Two series of 4-pyrrylamino quinazoline derivatives were designed and synthesized as new analogues of the EGFR inhibitor Gefitinib, with improved in vitro anti-tumor activity.

    4. Novel Naphthalimide–Benzoic Acid Conjugates as Potential Apoptosis-Inducing Agents: Design, Synthesis, and Biological Activity (pages 941–947)

      Aibin Wu, Ping Mei, Yufang Xu and Xuhong Qian

      Version of Record online: 29 SEP 2011 | DOI: 10.1111/j.1747-0285.2011.01232.x

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      A series of novel naphthalimide–benzoic acid conjugates were designed and synthesized. Their in vitro cytotoxicities and apoptosis–inducing activities were evaluated.

    5. QSAR Models for Phosphoramidate Prodrugs of 2′-Methylcytidine as Inhibitors of Hepatitis C Virus Based on PSO Boosting (pages 948–959)

      Zhengjun Cheng, Yuntao Zhang and Changhong Zhou

      Version of Record online: 31 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01236.x

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      In the paper, boosting regression has been proposed to model the activities of a series of phosphoramidate prodrugs of 2′-methylcytidine as inhibitors of hepatitis c virus. Eight QSAR models are established. The results have indicated the PSO-boosting method is a well-performing technique for developing new phosphoramidate prodrugs of 2′-methylcytidine. The squared correlation coefficient and standard deviation of the best model are 0.744 and 0.438 for the training set and 0.710 and 0.748 for the test set.

    6. 2D- and 3D-Quantitative Structure-Activity Relationship Studies for a Series of Phenazine N,N’-Dioxide as Antitumour Agents (pages 960–968)

      Jonathan Da Cunha, María Laura Lavaggi, María Inés Abasolo, Hugo Cerecetto and Mercedes González

      Version of Record online: 24 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01237.x

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      2D- and 3D-QSAR of phenazine N,N’-dioxide, Hypoxic selective cytotoxines estructure-activity relationship, Structural requirements of phenazine N,N’-dioxide as antitumoural drugs.

    7. Regioselective Synthesis of Novel 3-Thiazolidine Acetic Acid Derivatives from Glycosido Ureides (pages 969–978)

      Yuxin Li, Wei Chen, Xiaoping Yang, Guanping Yu, Mingzhen Mao, Yunyun Zhou, Tuanwei Liu and Zhengming Li

      Version of Record online: 24 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01241.x

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      A series of 3-thiazolidine acetic acid-2-(per-O-acetylglycosyl)-1′-imino-α-(substituted)-4-oxo ethyl ester derivatives (3a–t) were regioselectively synthesized from gylcosido ureides. The crystal structure of 3g and 1H-13C HMBC measurements of 3j revealed the exclusive regioselectivity during the closure of these rings towards the N-2 position of the thiourea moiety. The bioactivity data suggested that compound 2e has mild anti-cancer activity.

    8. Synthesis and Antifungal Activity of 1-[(2-Benzyloxy)Phenyl]-2-(Azol-1-yl)Ethanone Derivatives: Exploring the Scaffold Flexibility (pages 979–987)

      Saeed Emami, Motahare Kazemi-Najafabadi, Soughra Pashangzadeh, Alireza Foroumadi, Mohammad Ali Faramarzi, Nasrin Samadi, Mehraban Falahati, Roohollah Fateh and Mahtab Ashrafi-Khozani

      Version of Record online: 28 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01243.x

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      Based on the N-(phenethyl)azole backbone of azole antifungals, we designed 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives 2 and 3, containing benzyloxyphenyl scaffold of croconazole. Among the synthesized compounds, 1-[2-(2,4-dichlorobenzyloxy)phenyl]-2-(1H-imidazol-1-yl)ethanone hydrochloride (2g) showed comparable or more potent antifungal activity in comparison with fluconazole as a standard drug.

    9. Synthesis, In Vitro Antitubercular Activity and 3D-QSAR of Novel Quinoxaline Derivatives (pages 988–998)

      Ayarivan Puratchikody, Ramalakshmi Natarajan, Mohanapriya Jayapal and Mukesh Doble

      Version of Record online: 31 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01246.x

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      Novel quinoxaline derivatives are synthesised, screened for antitubercular activity and 3D-QSAR analysis was performed. The compounds with electron withdrawing group on the aromatic ring are found to be more active. QSAR studies indicated that the electrostatic and steric descriptors are negatively correlated with activity indicating that electronegative groups and less bulky groups would enhance activity.

  5. Research Letters

    1. Top of page
    2. Issue Information
    3. Editorial
    4. Review
    5. Research Articles
    6. Research Letters
    1. You have full text access to this OnlineOpen article
      Crizotinib-Resistant Mutants of EML4-ALK Identified Through an Accelerated Mutagenesis Screen (pages 999–1005)

      Sen Zhang, Frank Wang, Jeffrey Keats, Xiaotian Zhu, Yaoyu Ning, Scott D. Wardwell, Lauren Moran, Qurish K. Mohemmad, Rana Anjum, Yihan Wang, Narayana I. Narasimhan, David Dalgarno, William C. Shakespeare, Juan J. Miret, Tim Clackson and Victor M. Rivera

      Version of Record online: 31 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01239.x

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      A mutagenesis screen identified multiple mutations in the kinase domain that confer resistance to the first generation ALK inhibitor crizotinib. Our studies suggest that crizotinib’s low potency and narrow selectivity window for ALK may underlie its susceptibility to such resistance. These results provide guidance for the rational design and optimization of potent and selective second generation drugs that may be able to overcome ALK-based mechanisms of resistance.

    2. Design and Synthesis of a Series of Novel Bisquinazoline Glycosides as Epidermal Growth Factor Receptor Inhibitors (pages 1006–1013)

      Shaopeng Chen, Xiaowei Zhang, Junlei Wang, Shengbiao Wan, Meiyu Geng and Tao Jiang

      Version of Record online: 29 SEP 2011 | DOI: 10.1111/j.1747-0285.2011.01209.x

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      A new series of potential epidermal growth factor receptor (EGFR) inhibitors possessing bisquinazoline and saccharide moieties were designed. Of them, compound 14b showed the highest inhibitory rate towards EGFR protein tyrosine kinase (81.36%) at a concentration of 1 μm. Further molecular simulation predicted that 14b offered its saccharide moieties hydrogen bonding to ATP binding pocket.

    3. Kinetic Analyses of Keap1–Nrf2 Interaction and Determination of the Minimal Nrf2 Peptide Sequence Required for Keap1 Binding Using Surface Plasmon Resonance (pages 1014–1021)

      Yu Chen, Daigo Inoyama, Ah-Ng Tony Kong, Lesa J. Beamer and Longqin Hu

      Version of Record online: 31 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01240.x

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      An SPR-based solution competition assay was developed to determine the binding constants between Nrf2 peptides and Keap1 Kelch domain, and the minimal Nrf2 peptide sequence required for Keap1 binding. The minimal Nrf2 peptide sequence required is the 9mer Nrf2 peptide (LDEETGFEL) and its binding affinity to Keap1 Kelch domain was increased by 15-fold by acetylation of the N-terminal amino group.

    4. Novel Linear Diamine Disubstituted Polycyclic ‘Cage’ Derivatives as Potential Antimycobacterial Candidates (pages 1022–1030)

      Oluseye K. Onajole, Sphelele Sosibo, Patrick Govender, Thavendran Govender, Paul D. van Helden, Glenn E. M. Maguire, Kata Mlinarić-Majerski, Ian Wiid and Hendrik G. Kruger

      Version of Record online: 24 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01242.x

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      As part of an ongoing project to develop highly potent anti-tuberculosis therapeutics, a series novel polycyclic ‘cage’ tetra-amines were synthesized and screened for in-vitro anti-tuberculosis activities against the H37Rv strain of tuberculosis. Compounds 5 and 7 showed similar activity to SQ109 at a MIC of 1 μm while compounds 4, 6 and 8 displayed MIC activity at 1<MIC<10 μm against H37Rv strain of tuberculosis. Compounds 5 and 7 also showed excellent activity against MDR and XDR Tb strains.

    5. Synthesis and Antimycobacterial Activity of Novel Amino Alcohols Containing Central Core of the Anti-HIV Drugs Lopinavir and Ritonavir (pages 1031–1034)

      Claudia R. B. Gomes, Marcele Moreth, Danielle Cardinot, Valquiria Kopke, Wilson Cunico, Maria Cristina da Silva Lourenço and Marcus V. N. de Souza

      Version of Record online: 28 OCT 2011 | DOI: 10.1111/j.1747-0285.2011.01244.x

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      Three of the synthesized compounds showed more anti-TB activity than ethambutol.

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